Corrigendum: Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

[This corrects the article DOI: 10.3389/ti.2023.11589.].

Corrigendum: Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

[This corrects the article DOI: 10.3389/ti.2023.11590.].

Delphi: A Democratic and Cost-Effective Method of Consensus Generation in Transplantation.

The Thrombotic Microangiopathy Banff Working Group (TMA-BWG) was formed in 2015 to survey current practices and develop minimum diagnostic criteria (MDC) for renal transplant TMA (Tx-TMA). To generate consensus among pathologists and nephrologists, the TMA BWG designed a 3-Phase study. Phase I of the study is presented here. Using the Delphi methodology, 23 panelists with >3 years of diagnostic experience with Tx-TMA pathology listed their MDC suggesting light, immunofluorescence, and electron microscopy lesions, clinical and laboratory information, and differential diagnoses. Nine rounds (R) of consensus resulted in MDC validated during two Rs using online evaluation of whole slide digital images of 37 biopsies (28 TMA, 9 non-TMA). Starting with 338 criteria the process resulted in 24 criteria and 8 differential diagnoses including 18 pathologic, 2 clinical, and 4 laboratory criteria. Results show that 3/4 of the panelists agreed on the diagnosis of 3/4 of cases. The process also allowed definition refinement for 4 light and 4 electron microscopy lesions. For the first time in Banff classification, the Delphi methodology was used to generate consensus. The study shows that Delphi is a democratic and cost-effective method allowing rapid consensus generation among numerous physicians dealing with large number of criteria in transplantation.

Thrombotic Microangiopathy in the Renal Allograft: Results of the TMA Banff Working Group Consensus on Pathologic Diagnostic Criteria.

The Banff community summoned the TMA Banff Working Group to develop minimum diagnostic criteria (MDC) and recommendations for renal transplant TMA (Tx-TMA) diagnosis, which currently lacks standardized criteria. Using the Delphi method for consensus generation, 23 nephropathologists (panelists) with >3 years of diagnostic experience with Tx-TMA were asked to list light, immunofluorescence, and electron microscopic, clinical and laboratory criteria and differential diagnoses for Tx-TMA. Delphi was modified to include 2 validations rounds with histological evaluation of whole slide images of 37 transplant biopsies (28 TMA and 9 non-TMA). Starting with 338 criteria in R1, MDC were narrowed down to 24 in R8 generating 18 pathological, 2 clinical, 4 laboratory criteria, and 8 differential diagnoses. The panelists reached a good level of agreement (70%) on 76% of the validated cases. For the first time in Banff classification, Delphi was used to reach consensus on MDC for Tx-TMA. Phase I of the study (pathology phase) will be used as a model for Phase II (nephrology phase) for consensus regarding clinical and laboratory criteria. Eventually in Phase III (consensus of the consensus groups) and the final MDC for Tx-TMA will be reported to the transplantation community.

Screening for polyomavirus nephropathy and viremia in children with renal transplantation.

BACKGROUND: Polyomavirus, known as BK virus, is an important cause of allograft dysfunction in renal transplant patients, leading to BK virus nephropathy. The main study objectives were to assess the disease incidence and disease course in pediatric patients, and assess the diagnostic accuracy of BK screening for asymptomatic patients. METHODS: This is a single-center observational study, which included 81 pediatric renal allograft recipients that were transplanted and/or followed at King Fahad Specialist Hospital-Dammam, Saudi Arabia. Screening for BK virus was performed prospectively according to a predetermined hospital protocol. Our BK screening protocol consisted of periodic quantitative real time polymerase chain reaction test in the plasma. In patients with deranged graft function, graft biopsies were evaluated for the presence of BK nephropathy. RESULTS: Our study detected BK viremia in 14 patients (17.3%), while BK nephropathy occurred in seven patients (8.6%). The onset of BK viremia had bimodal distribution, 78 percent occurring within first year post-transplantation, while 21.4% occurred late. Patients who developed BK nephropathy had a higher BK level than BK viremia patients, for both mean and peak values (p = .02, p = .02). A BK cutoff level of 40 000 copies/mL showed sensitivity and specificity of 85.7%, 85.7%, respectively, in predicting the conversion of BK viremia to BK nephropathy. CONCLUSIONS: BK viremia and BK nephropathy occur in pediatric patients with similar incidence rates compared to adult patients. Protocolized screening led to early detection of viremia, and could predict the conversion of BK viremia to BK nephropathy and allow for early immunosuppression modulation.

Severe delayed graft function in a living-related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report.

BACKGROUND: Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non-HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen-related antigens as well unrelated antigens is common post-viral infection. In transplant-setting induction of heterologous immunity that cross-react with HLA-antigens and subsequent reactivation of memory T cells can lead to allograft rejection. METHODS: Here we describe a non-sensitized child with ESRD secondary to lupus nephritis and recent history of COVID-19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA-haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody-mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre- and post-transplant sera showed very high level of several non-HLA antibodies. RESULTS: The patient was treated for cellular and antibody-mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. CONCLUSION: The cellular rejection likely trigged by ischemia that activated T-cells-mediated immunity. The high level of non- HLA-antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T-cell activation induced by heterologous immunity.

Donor Kidney Evaluation.

In patients with end-stage renal disease, kidney transplantation is the best means to extend survival and offer a better quality of life. The current shortage of organs available for transplantation has led to an effort to expand the kidney donor pool, including the use of nonideal donor kidneys. Assessment of the quality of the donated kidney is essential, and would facilitate the decision to transplant a potential organ or discard it. Multiple clinical and histologic parameters have been examined to evaluate the donor kidney and relate the findings to the graft outcome, but clear-cut criteria are yet to be defined.

Renal Amyloidosis.

Amyloidosis is an uncommon group of diseases in which soluble proteins aggregate and deposit extracellularly in tissue as insoluble fibrils, leading to tissue destruction and progressive organ dysfunction. More than 25 proteins have been identified as amyloid precursor proteins. Amyloid fibrils have a characteristic appearance on ultrastructural examination and generate anomalous colors under polarized light. Amyloidosis can be systemic or localized. The kidney is a prime site for amyloid deposition. Immunofluorescence, immunoperoxidase, and more recently laser microdissection and mass spectrometry are important tools used in the typing of renal amyloidosis.

ANCA-associated vasculitis in systemic sclerosis report of 3 cases.

The aim of the study was to describe the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in systemic sclerosis (SSc) patients. SSc patients who developed biopsy-proven AAV were identified. Their clinical manifestations, autoantibodies, presentation with vasculitis, treatment and outcome were described and compared with previously reported patients with these two conditions. Of 985 patients, 3 were identified. All patients had interstitial lung disease, and all presented with acute renal failure, proteinuria and hematuria, and were P-ANCA- and anti-Scl-70-positive. One required hemodialysis. Two were hypertensive; additionally, one patient had sinusitis, and another had monoarthritis and a macular rash. All were treated with high-dose corticosteroids and responded to therapy and attained remission at 6 months. At 1 year, one patient died of pneumonia. ANCA-associated vasculitis is a rare but serious finding in SSc patients. Positive anti-Scl-70 antibody is found commonly in these patients. Different treatment modalities are effective. Serious infections can complicate therapy and lead to death.

Collapsing glomerulopathy following anthracycline therapy.

We report 2 cases of anthracycline-induced collapsing glomerulopathy, one in a patient treated for peripheral T-cell lymphoma, and the other in a kidney transplant recipient treated for acute myeloid leukemia. Collapsing glomerulopathy is a distinct variant of focal segmental glomerulosclerosis (FSGS) that has been attributed to several different causes besides human immunodeficiency virus (HIV) in recent years. Previously, anthracycline use has been associated with FSGS, not otherwise specified (NOS). However, in the absence of therapy, various hematolymphoid malignancies have been associated with FSGS, NOS and collapsing glomerulopathy. In individuals who have hematolymphoid malignancy or are being treated with an anthracycline, the frequency of FSGS is extremely low. We suggest that in the following 2 patients, anthracycline use caused collapsing FSGS based on the temporal relationship, but also in the context of potentially underlying predisposing conditions. Host and environmental factors may interact to cause one morphologic form of FSGS or another.

Use of renal biopsy in the elderly.

Renal biopsy is an essential tool in the management of kidney disease. A biopsy provides a diagnosis, guides therapy and aids in prognosis, and this is true for persons of all ages. For a variety of reasons, nephrologists are sometimes hesitant to perform a biopsy in an older person. There is the major issue of a lack of perceived benefit that the biopsy will not show a treatable lesion and that therapy may not be possible in an older person. Additionally, concerns of safety may also influence the decision to biopsy. In this review, we will address these issues in the context of clinical renal syndromes and common kidney diseases in the elderly and weigh the benefit of biopsy in various situations. In general, the indications are the same as in the adult population, as is the risk associated with the biopsy procedure. Therapy, as for adults, is often successful, although further assessment of risk-benefit ratio is necessary. Age, by itself, is not a contraindication to biopsy.